The tumour microenvironment creates a niche for the self-renewal of tumour-promoting macrophages in colon adenoma

• Main Authors: Soncin, Irene, Sheng, Jianpeng, Chen, Qi, Foo, Shihui, Duan, Kaibo, Lum, Josephine, Poidinger, Michael, Zolezzi, Francesca, Karjalainen, Klaus, Ruedl, Christiane
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2018
• Online Access: https://hdl.handle.net/10356/89512; http://hdl.handle.net/10220/44929; https://doi.org/10.21979/N9/EQXCRF
• Institution: Nanyang Technological University

Circulating CCR2+ monocytes are crucial for maintaining the adult tissue-resident F4/80hiMHCIIhi macrophage pool in the intestinal lamina propria. Here we show that a subpopulation of CCR2-independent F4/80hiMHCIIlow macrophages, which are the most abundant F4/80hi cells in neonates, gradually decline in number in adulthood; these macrophages likely represent the fetal contribution to F4/80hi cells. In colon adenomas of ApcMin/+ mice, F4/80hiMHCIIlow macrophages are not only preserved, but become the dominant subpopulation among tumour-resident macrophages during tumour progression. Furthermore, these pro-tumoural F4/80hiMHCIIlow and F4/80hiMHCIIhi macrophages can self-renew in the tumour and maintain their numbers mostly independent from bone marrow contribution. Analyses of colon adenomas indicate that CSF1 may be a key facilitator of macrophage self-renewal. In summary, the tumour microenvironment creates an isolated niche for tissue-resident macrophages that favours macrophage survival and self-renewal.